title: Role of toxicogenomics in the development of safe, efficacious and novel anti-microbial therapies.
abstract: Over the last two decades, occurrence of bacterial resistance to commonly used antibiotics has necessitated the development of safer and more potent anti-microbial drugs. However, the development of novel antibiotics is severely hampered by adverse side effects, such as drug-induced liver toxicity. Several antibacterial drugs are known to have the potential to cause severe liver damage. The major challenge in developing novel anti-microbial drugs is to predict, with certain amount of probability, the drug-induced toxicity during the pre-clinical stages, thus optimizing and reducing the time and cost of drug development. Toxicogenomics approach is generally used to harness the potential of genomic tools and to understand the physiological basis of drug-induced toxicity based on the in-depth analysis of Metagenomic data sets, i.e., transcriptional, translational or metabolomic profiles. Toxicogenomics, therefore, represents a new paradigm in the drug development process, and is anticipated to play an invaluable role in future to develop safe and efficacious medicines, by predicting the toxic potential of a new chemical entity (NCE) in early stages of drug discovery. This review examines the toxicogenomic approach in predicting the safety/toxicity of novel anti-microbial drugs, and analyses the promises, pitfalls and challenges of applying this powerful technology to the drug development process.
authors.affiliation: Department of Biology, Faculty of Science, King Abdulaziz University, P.O. Box 80203 Jeddah 21589, Saudi Arabia. ksaini@kau.edu.sa.
authors.forename: Jamal S M
authors.initials: JS
authors.lastname: Sabir
authors.forename: Osama A
authors.initials: OA
authors.lastname: Abu-Zinadah
authors.forename: Roop S
authors.initials: RS
authors.lastname: Bora
authors.forename: Mohamed M M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Kulvinder S
authors.initials: KS
authors.lastname: Saini
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D004345:Drug Industry / Q000379:methods* / Q000639:trends; D018432:Drug Resistance, Multiple; D015507:Drugs, Investigational / Q000009:adverse effects* / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control; D018675:Toxicity Tests / Q000379:methods* / Q000639:trends; D043922:Toxicogenetics / Q000379:methods*
chemical_list: D000890:Anti-Infective Agents; D015507:Drugs, Investigational